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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 937 records · Page 52Linked to original sources
PubMed1998

Nuclear targeting of the serine protease granzyme A (fragmentin-1).

Cytolytic granule-mediated target cell killing is effected in part through synergistic action of the membrane-acting protein perforin and serine proteases such as granzymes A (GrA) or B (GrB). In the present study we examine GrA cellular entry and nuclear uptake in intact mouse myeloid FDC-P1 cells exposed to perforin using confocal laser scanning microscopy, as well as reconstitute GrA nuclear uptake in vitro. GrA alone was found to be able to enter the cytoplasm of intact cells but did not accumulate in nuclei. In the presence of perforin, it specifically accumulated in the cell nuclei, with maximal levels about 2.5 times those in the cytoplasm after 2. 5 hours. In vitro, GrA accumulated in the nucleus and nucleolus maximally to levels that were four- and sixfold, respectively, those in the cytoplasm. In contrast, the active form of the apoptotic cysteine protease CPP32 did not accumulate in nuclei in vitro. Nuclear/nucleolar import of GrA in vitro was independent of ATP and not inhibitable by the non-hydrolyzable GTP analog GTPgammaS, but was dependent on exogenously added cytosol. Importantly, GrA was found to be able to accumulate in the nucleus of semi-intact cells in the presence of the nuclear envelope-permeabilizing detergent CHAPS, implying that the mechanism of nuclear accumulation was through binding to insoluble factors in the nucleus. GrB was found for the first time to be similar in this regard. The results support the contention that GrA and GrB accumulate in the nucleus through a novel nuclear import pathway, and that this is integral to induction of the nuclear changes associated with cytolytic granule-mediated apoptosis.

Adenosine Triphosphate↗
PubMed1998

Inhibition of succinic semialdehyde dehydrogenase by N-formylglycine.

N-formylglycine was developed as a dead-end inhibitor of the succinic semialdehyde dehydrogenase reaction. At 4 mM, it inhibited Aspergillus niger succinic semialdehyde dehydrogenase by 40%. N-formylglycine is a reversible, complete inhibitor; the inhibition is competitive with succinic semialdehyde and uncompetitive with respect to NAD+ and the Ki values are 4.9 and 10.4 mM respectively. Potato succinic semialdehyde dehydrogenase is also inhibited by N-formylglycine to a similar extent, the nature of the inhibition being identical to that observed with the A. niger enzyme.

Aldehyde Oxidoreductases↗
PubMed1998

An outbreak of cyclosporiasis in Florida in 1995: a harbinger of multistate outbreaks in 1996 and 1997.

Before 1995, only one outbreak of cyclosporiasis had been reported in the United States. To identify risk factors for Cyclospora infection acquired in Florida in 1995, we conducted a matched case-control study (24 sporadic cases and 69 controls) and retrospective cohort studies of clusters of cases associated with two May social events (attack rates = 15.4% [8 of 52] and 54.5% [6 of 11]). In univariate analysis of data from the case-control study, consumption of fresh raspberries (odds ratio [OR] = 6.0, 95% confidence interval [CI] = 1.1-31.7) and bare-handed contact with soil (OR = 5.4, 95% CI = 1.4-20.7) were associated with infection; soil contact was also implicated in multivariate analysis. For the events, mixed-fruit items that had only fresh raspberries and strawberries in common had elevated relative risks (3.7 and 4.2), but the confidence intervals overlapped 1.0. The raspberries eaten at the events and by sporadic case-patients were imported. Given the cumulative evidence of the three studies and the occurrence in 1996 and 1997 of outbreaks in North America associated with consumption of Guatemalan raspberries, food-borne transmission of Cyclospora was likely in 1995 in Florida as well.

Adolescent↗
PubMed1998

Humoral immune responses against Plasmodium vivax MSP1 in humans living in a malaria endemic area in Flores, Indonesia.

The aim of this study was to evaluate the relationship among age, parasitemia status, spleen size, hematocrit, and antibody levels to Plasmodium vivax merozoite surface protein 1 (MSP1) in individuals chronically exposed to P. vivax. Subjects were recruited from the population of three adjacent villages on the Island of Flores in Indonesia where malaria transmission is hyperendemic and tropical splenomegaly syndrome is highly prevalent. Subjects were evaluated for spleen size, hematocrit, presence of parasitemia, and presence of antibodies to a recombinant peptide consisting of 90 amino acids from the carboxy terminus of MSP1. Fifty-seven percent of 2-4 year olds, 45% of 5-9 years old, and 7% of > or = 15 years old were parasitemic; 99% of the > or = 15 years old had splenomegaly, and 31% of them had Hackett 4 or 5 spleens. The frequency of antibody positivity to MSP1 antigen in ELISA increased with age reaching a maximum of 89% in > or = 20 years old. The frequency of antibody positivity to MSPI also increased with spleen size, and with a decline in the prevalence of parasitemia.

Adolescent↗
PubMed1998

Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study.

Two hundred and twenty five patients of Takayasu's arteritis were studied over 13 years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4 years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac involvement and these patients were subjected to coronary angiography. Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal diameter) was present in 9 patients. Incidence of coronary artery lesions in Takayasu's arteritis is 12% in this study. The proximal segments of coronary arteries were involved while the distal segments were spared. Out of 34 patients with angina pectoris, only 3 patients had significant coronary arterial narrowing.

Adolescent↗
PubMed1998

Overnight corneal swelling in symptomatic and asymptomatic contact lens wearers.

PURPOSE: High corneal swelling with contact lens wear may be a predictor of patient failure in overnight contact lens use. This study evaluated whether contact lens wearers who had previously experienced corneal inflammation showed greater corneal swelling following a single occasion of overnight contact lens use compared with matched controls. METHODS: Forty-four subjects were evaluated: 9 wearers who had experienced contact lens associated acute red eye (CLARE); 9 controls; 13 subjects who had experienced contact lens induced peripheral ulcer (CLPU); and 13 controls. Controls were matched to cases for age, gender, wear experience and refractive error. Subjects wore bilateral disposable contact lenses overnight. Central corneal thickness was measured optically using a Holden-Payor pachometer at baseline, on eye opening, and 1, 2, and 4 hours later. RESULTS: There was no significant difference in overnight corneal swelling between CLARE subjects (7.6 +/- 2.3%) and controls (7.0 +/- 2.3%) (P = 0.57). Similarly, there was no significant difference in overnight corneal swelling between CLPU subjects (7.7 +/- 2.2%) and controls (7.8 +/- 2.6%) (P = 0.89). Deswell rate was similar in all groups. CONCLUSIONS: There was no apparent predisposition for higher overnight corneal swelling or altered deswell rate after one night of lens wear in subjects who had previously experienced contact lens related corneal inflammation.

Adult↗
PubMed1998

Prevalence & etiology of nutritional anaemias in early childhood in an urban slum.

The present study was carried out to find out the prevalence and etiology of nutritional anaemia among preschool children from an urban slum. Randomly selected 300 children aged 3 months-3 yr were analysed over a period of one year for estimating prevalence of nutritional anaemia. Prevalence was also assessed by the rise in haemoglobin after 8 wk of haematinic supplementation in 159 of the 300 subjects. Ninety anaemic children were evaluated for the etiology of anaemia. Prevalence of anaemia, as judged by WHO recommended 'cut-off' value of haemoglobin < 11 g/dl, was 76 per cent while comparable value of 74.8 per cent was derived by response to haematinic supplementation. Pure iron deficiency anaemia (IDA) was detected in 41.4 per cent (37/90) of anaemic children. Vitamin B12 deficiency alone or in combination with iron was diagnosed in 14.4 and 22.2 per cent anaemic children respectively. Similarly folate deficiency, IDA with infection and anaemia of chronic diseases (ACD) was diagnosed in 2.2, 3.3 and 12.2 per cent cases respectively. Childhood anaemia continues to be a significant public health problem in preschoolers and iron deficiency is by far the commonest nutritional cause of anaemia. Vitamin B12 deficiency per se or in combination with iron is an important yet not commonly recognised cause of anaemias in preschool children in the community.

Anemia↗
PubMed1998

Urinary net charge in hyperchloremic metabolic acidosis.

OBJECTIVE: (i) To examine the usefulness of urinary net charge (UNa + UK - UCl) in the evaluation of hyperchloremic metabolic acidosis secondary to diarrhea, distal RTA and proximal RTA and (ii) To characterize the type of distal RTA on the basis of the underlying defect. SETTING: Pediatrics division of a tertiary referral center. SUBJECTS: Thirty four children with hyperchloremic metabolic acidosis secondary to diarrhea (n = 16), distal RTA (n = 11) and proximal RTA (n = 7). Ten normal children with ammonium chloride induced acidosis were also studied. METHODS: All subjects underwent urine collection of 30-60 minutes duration for measurement of Na, K, Cl, pH and pCO2. The measurements were also made on the blood samples collected at the midpoint of urine collection. The urinary net charge was calculated by subtracting Cl values from the sum of the Na and K. RESULTS: Patients with proximal and distal RTA had a positive urine net charge. Patients with diarrhea and ammonium chloride induced acidosis showed negative urine net charge. Patients with diarrhea with extremely low urine sodium levels showed an inappropriately high urine pH despite persistent metabolic acidosis. All patients with distal RTA were found to have a secretory type of defect. CONCLUSION: Measurement of urine net charge is helpful in the initial evaluation of a patient with hyperchloremic metabolic acidosis.

Acidosis↗
PubMed1998

Angiogenic oligosaccharides of hyaluronan induce protein tyrosine kinase activity in endothelial cells and activate a cytoplasmic signal transduction pathway resulting in proliferation.

We have recently shown that the degradation products of hyaluronan of 3 to 10 disaccharides (o-HA), but not native high molecular weight hyaluronan, can induce angiogenesis in vivo and, as such, o-HA is an important regulator of the neovascularization process. As a continuation of this work, we have studied the cytoplasmic signal transduction pathways responsible for o-HA-activated endothelial cell proliferation. We show that the addition of o-HA (1 microg/ml) to bovine aortic endothelial cells induces tyrosine phosphorylation of multiple proteins within 1 minute and that the activity remains above basal levels for at least 24 hours. Increased phosphorylation of the CD44 receptor was also observed. Pretreatment of cells with an anti-CD44-receptor antibody (5 microg/ml) or the tyrosine kinase inhibitor genistein (10 microM) inhibited both o-HA-induced proliferation (p < 0.05) and protein tyrosine phosphorylation. In comparison, native hyaluronan had little effect on tyrosine phosphorylation across the same time period. Protein kinase C (PKC) activity was increased 2- to 3-fold in the membranes of cells treated with o-HA, and a pretreatment with phorbol 12,13-dibutyrate (PDBu) to down-regulate PKC significantly inhibited o-HA-induced cell proliferation (p < 0.05). Examination by Western blotting showed that only the betaI and epsilon isoforms remained translocated to the membrane for at least 24 hours. These isoforms seem to be involved in modulating the proliferative effects of o-HA, because the transient translocation of PKC isoforms by PDBu was not sufficient to induce mitogenesis. Furthermore, we show that PKC activation of the cytoplasmic kinase cascade (Raf-1 kinase, MAP kinase kinase [MEK-1], and extracellular signal-regulated kinase [ERK-1]) by o-HA culminated in the nuclear translocation of ERK-1. This pathway is essentially linear, as shown by the ability of specific enzyme inhibitors (PDBu and PD98059) to prevent both activation of ERK-1- and o-HA-induced proliferation. We conclude that phosphorylation of the CD44 receptor results in an increase in tyrosine phosphorylation, leading to the activation of a cytoplasmic cascade and cell proliferation; this concurs with previous work, which showed that o-HA-induced proliferation of endothelial cells is CD44-receptor-mediated and accompanied by early response gene activation.

Animals↗
PubMed1998

Effect of sodium on Saccharomyces cerevisiae invertase activity.

Effect of Na+ ions on yeast invertase activity has been studied as a function of pH. At acidic pH, Na+ (5-100 mM) had no effect but invertase activity was inhibited (38-44%) by Na+ ions (100 mM) with an increase in pH (6.8 and 8.0). Kinetic analysis revealed that invertase inhibition by Na+ ions was non-competitive and reversible in nature. Value of K(m) remained unaltered (33.3 mM) in presence of Na+ (20-100 mM) while Vmax decreased by 21-44% under these conditions. Value of Ki was of the order of 85 mM. Mechanism of observed inhibition of invertase activity as a consequence of Na+ ions interactions at the active site of the enzyme has been described.

Glycoside Hydrolases↗